Oncology drug lag in Japan is improving significantly

Nearly every oncology drug in development in Japan is also in development in the United States and Europe according to the most recent edition of Kantar Health’s Treatment Evolution, Japan, published in early 2011.1 This is an improvement from the first edition of Treatment Evolution, Japan, published in 2006, where drug lag in Japan was still a severe issue. In the most recent edition, the majority of drugs developed by companies headquartered in the United States or Europe also are being developed in Japan, which could take the form of:

1. A Phase III trial enrolling patients from many countries, including Japan

2. A Phase II bridging study ongoing in Japan to pair with a Western Phase III

3. A Phase I trial in Japan that could signal future involvement in a global Phase III or the future initiation of a bridging study

Drug lag is loosely defined as the delay between Japan and the West (Europe and the United States) in approving drugs, for example in cancer. With many developers’ current development plans to include Japanese patients in global Phase III trials, drug lag will no longer be a factor in many cancers, including gastric, non-small cell lung, breast, colorectal, hepatocellular carcinoma, and chronic myelogenous leukemia.

“…the average difference between drug launches in Western countries and Japan was more than 3.5 years before the recent era of targeted therapy.”

According to the Japanese Pharmaceutical Manufacturers Association, the average difference between drug launches in Western countries and Japan was more than 3.5 years before the recent era of targeted therapy. Support from the Ministry of Health, Labor, and Welfare (MHLW or the Ministry), the regulatory agency that approves drugs in Japan, has improved drug lag in several ways:

• The Ministry established the Study Council on the Use of Unapproved Drugs in 2006 to accelerate the launch of important new drugs.

• The Council has encouraged companies to start trials for drugs already approved in the West but not yet approved in Japan. It also encouraged Japanese participation in global Phase III trials or at least the initiation bridging studies in Japan alongside Phase III trials in Western regions.

• The Council has made recommendations for the approval of drugs based on data in the “public domain.”

“The Japanese oncology market has witnessed the approval or filing for approval of several drugs identified by the Council with severe drug lag.”

The Japanese oncology market has witnessed the approval or filing for approval of several drugs identified by the Council with severe drug lag. These approvals were allowed by the Council on the Use of Unapproved Drugs based on data in the “public domain” without a formal completion of a bridging study. Examples include Hycamtin® (topotecan, GlaxoSmithKline, already approved for lung cancer) for ovarian cancer, Gemzar® (gemcitabine, Eli Lilly and Company, already approved for pancreatic and lung cancer) for ovarian and breast cancer, and Xeloda® (capecitabine, Roche/Chugai, already approved for breast and colorectal cancer) for gastric cancer. The approvals essentially “cleared the slate” on the difference in drug availability in Japan compared with the West in two cancers.

Drug lag has been improving with the increase in Japanese participation in global Phase III trials. A recent example of inclusion of Japanese patients in a pivotal global Phase III trial is the RECORD study, which compared Afinitor® (everolimus, Novartis) to placebo in renal cell carcinoma patients previously treated with Sutent® (sunitinib, Pfizer) or Nexavar® (sorafenib, Onyx/Bayer). Afinitor was approved in Japan (January 2010) less than a year after approvals in Europe (August 2009) and the United States (March 2009). Comparatively, both Sutent and Nexavar were approved in Japan after the completion of a bridging study approximately 15-24 months after approvals in the United States and Europe. Torisel® (temsirolimus, Pfizer) was approved in Japan 33-36 months after approvals in the United States and Europe.

Bridging studies do not necessarily limit approval times in Japan if the bridging study is completed near the same time as the Western Phase III trial is complete. The best example of this is Halaven® (eribulin, Eisai). Eisai filed Halaven simultaneously in the United States, Europe, and Japan in March 2010. Approval is expected in Japan the second quarter of 2011, less than three months after approval in Europe and less than six months after approval in the United States. This would represent the shortest drug lag in recent history.

“Drug lag has been improving with the increase in Japanese participation in global Phase III trials.”

Drug lag could still be a problem in certain cancers. For example, highly active agents such as Velcade® (bortezomib, Takeda/Janssen) and Revlimid® (lenalidomide, Celgene) are not available currently for first-line use in Japan. This might partially change with the filing of Velcade for first-line use in late 2010 and evidence of the inclusion of Japanese patients in global Phase III trials for several agents in development for relapsed or refractory multiple myeloma. Erbitux® (cetuximab, Eli Lilly and Company / Bristol-Myers Squibb / Merck Serono, already approved for colorectal cancer), is still not approved in Japan for head and neck cancer 3 years after approval in the United States, although bridging studies are ongoing. In addition to multiple myeloma, Kantar Health observed a mix of drug lag and global participation in Phase III trials in brain cancer and non-Hodgkin’s lymphoma.

References

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About the author:

Gordon Gochenauer is the Director of CancerMPact® at Kantar Health. CancerMPact® Treatment Evolution explores potential changes in treatment practices based on a critical evaluation of recently published clinical data, regulatory advances and setbacks, and ongoing clinical trials. These implications shed light on the potential trends and events that can pose threats or opportunities to agents in development. This report also discusses areas of high unmet need which may represent specific opportunities for new drug development.

Kantar Health are experts in pharmaceutical and biotechnology consulting and market research, offering unique, proven solutions for marketing insights, brand marketing, business development and health economics/outcomes professionals. We combine scientific and business expertise to ensure evidence-based and commercially focused solutions for both emerging and established markets and spanning the product life cycle.